Uninary tract infection (UTI) is one of the most common bacterial infections in developed countries; hospital acquired UTI is the most frequent nosocomial infection. Escherichia coli is the most frequent cause of both community- and hospital-acquired UTI. Uropathogenic E. coli possess virulence associated factors not as frequently found among fecal E. coli isolates. The long term goals of this of this research are to identify new methodologies for the prevention and treatment of UTI by E. coli, by acquiring a more thorough understanding of its pathogenic mechanisms. The immediate objectives of this project are to identify those bacterial factors which are both necessary and sufficient for E. coli to colonize the mouse urinary tract in an ascending model of pyelonephritis. The results of our experiments have demonstrated the necessities for P- and type-1 fimbriae, and the polysaccharide antigens o and K in the capacity of E. coli to colonize the mouse UT. In this application we propose to clone the genes for O and k antigen synthesis to further quantify their roles in virulence. Recombinant plasmids encoding the enzymes required for the synthesis of these polysaccharides will be transferred to a nonpathogenic laboratory E. coli strain, and the various isogenic transformants will be compared with respect to (1) resistance to the bactericidal effects of serum, and to ingestion by phagocytes, and (2) capacity to colonize the UT of mice. Mouse infection studies will be performed by Dr. Catharina Svanborg-Eden, University of Goteborg, Sweden. Furthermore, we have discovered that P-fimbriae are not identical with respect to receptor recognition. Recombinant plasmids encoding the three different types of P-fimbriae will be constructed (only one remains to be subcloned) and transferred to a nonpathogenic fecal isolate of E. coli to test the relative capacities of each type of infect mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI021009-04
Application #
3130898
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1984-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Hull, R A; Nowicki, B; Kaul, A et al. (1994) Effect of pap copy number and receptor specificity on virulence of fimbriated Escherichia coli in a murine urinary tract colonization model. Microb Pathog 17:79-86
Klann, A G; Hull, R A; Palzkill, T et al. (1994) Alanine-scanning mutagenesis reveals residues involved in binding of pap-3-encoded pili. J Bacteriol 176:2312-7
Batchelor, R A; Alifano, P; Biffali, E et al. (1992) Nucleotide sequences of the genes regulating O-polysaccharide antigen chain length (rol) from Escherichia coli and Salmonella typhimurium: protein homology and functional complementation. J Bacteriol 174:5228-36
Klann, A G; Hull, R A; Hull, S I (1992) Sequences of the genes encoding the minor tip components of Pap-3 pili of Escherichia coli. Gene 119:95-100
Ding, M J; Svanborg, C; Haraguchi, G E et al. (1991) Molecular cloning and expression of the 01 rfb region from a pyelonephritic Escherichia coli 01:H1:K7. Microb Pathog 11:379-85
Batchelor, R A; Haraguchi, G E; Hull, R A et al. (1991) Regulation by a novel protein of the bimodal distribution of lipopolysaccharide in the outer membrane of Escherichia coli. J Bacteriol 173:5699-704
Haraguchi, G E; Zahringer, U; Jann, B et al. (1991) Genetic characterization of the O4 polysaccharide gene cluster from Escherichia coli. Microb Pathog 10:351-61
Nowicki, B; Runyan, R S; Smith, N et al. (1990) Kinetics of colonization of a porous vitreous carbon percutaneous implant. Biomaterials 11:389-92
Karr, J F; Nowicki, B J; Truong, L D et al. (1990) pap-2-encoded fimbriae adhere to the P blood group-related glycosphingolipid stage-specific embryonic antigen 4 in the human kidney. Infect Immun 58:4055-62
Nowicki, B; Labigne, A; Moseley, S et al. (1990) The Dr hemagglutinin, afimbrial adhesins AFA-I and AFA-III, and F1845 fimbriae of uropathogenic and diarrhea-associated Escherichia coli belong to a family of hemagglutinins with Dr receptor recognition. Infect Immun 58:279-81

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